title: Conditional ablation of Gata4 and Fog2 genes in mice reveals their distinct roles in mammalian sexual differentiation.
abstract: Assembly of functioning testis and ovary requires a GATA4-FOG2 transcriptional complex. To define the separate roles for GATA4 and FOG2 proteins in sexual development of the testis we have ablated the corresponding genes in somatic gonadal cells. We have established that GATA4 is required for testis differentiation, for the expression of Dmrt1 gene, and for testis cord morphogenesis. While Sf1Cre-mediated excision of Gata4 permitted normal expression of most genes associated with embryonic testis development, gonadal loss of Fog2 resulted in an early partial block in male pathway and sex reversal. We have also determined that testis sexual differentiation is sensitive to the timing of GATA4 loss during embryogenesis. Our results now demonstrate that these two genes also have non-overlapping essential functions in testis development.
authors.affiliation: Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Manuylov
authors.forename: B
authors.initials: B
authors.lastname: Zhou
authors.forename: Q
authors.initials: Q
authors.lastname: Ma
authors.forename: S C
authors.initials: SC
authors.lastname: Fox
authors.forename: W T
authors.initials: WT
authors.lastname: Pu
authors.forename: S G
authors.initials: SG
authors.lastname: Tevosian
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D005260:Female; D050991:GATA4 Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D024282:Genes, sry; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010053:Ovary / Q000196:embryology; D055758:SOX9 Transcription Factor / Q000235:genetics; D012708:Sertoli Cells / Q000378:metabolism; D012733:Sex Differentiation / Q000235:genetics / Q000502:physiology*; D013737:Testis / Q000196:embryology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: C110547:DMRT1 protein; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; C492170:Zfpm2 protein, mouse